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KEY CONCEPTS

  • Gastric cancer remains the third most common cause of cancer-related death worldwide.

  • Two different pathogeneses of gastric cancer have been proposed, correlating to two histologic types: intestinal and diffuse.

  • Gastrectomy is the recommended treatment in relatively early localized gastric cancer (T1b); however, in more advanced gastric cancers (T2N0, T1aN+, or T1b-T3N+), adjunctive therapy in addition to gastrectomy is recommended.

  • The results of INT-0116 study (adjuvant chemoradiation) and Medical Research Council ST02/MAGIC and the FLOT study (perioperative chemotherapy) have shaped the current practice of resectable gastric cancer treatment in Western countries.

  • In Asia, postoperative chemotherapy has been considered standard after gastrectomy with D2 dissection. In addition to the ACTS-GC trial and CLASSIC trial (S-1 for 1 year and CAPOX for 6 months, respectively), two new regimens (DS and SOX for 6 months) are established standards of care for stage II and/r LN-positive gastric cancer.

  • Only 30% to 40% of patients with esophageal cancer have potentially resectable disease at presentation, and in many series, only 5% to 20% of those undergoing surgery alone for clinically localized disease are alive at 3 to 5 years.

  • Endoscopic therapy is most effective when used to treat small (<2 cm diameter), solitary, flat lesions that are confined to mucosa (T1a).

  • Surgery remains the best chance for durable survival for patients with locally advanced esophageal and gastroesophageal junction (GEJ) cancers.

  • Results of the CROSS trial also emphasized the beneficial role of chemoradiotherapy before surgery, which led to a significant increase in overall survival (OS) irrespective of tumor histology.

  • More than 60% of patients who present with newly diagnosed gastric, GEJ, and esophageal cancers will have advanced unresectable or metastatic disease. Although a cure is not possible, systemic therapy can prolong survival compared with best supportive care.

  • As of this writing, patients in the United States are likely to undergo frontline therapy with platinum-, fluoropyrimidine-, or taxane-based chemotherapy regimens, with the addition of trastuzumab in patients with HER2-positive disease.

  • Based on positive results from the RAINBOW trial, paclitaxel and ramucirumab (vascular endothelial growth factor receptor–2 targeted drug) is considered to be a standard for second-line treatment. Ramucirumab monotherapy is also considered a second-line option in advanced gastric cancer.

  • Pembrolizumab is currently approved for the treatment of metastatic squamous cell carcinoma (SCC) of the esophagus as second-line treatment for tumors with combined positive score (CPS) more than 10 and programmed cell death protein 1 (PD-L1)–positive advanced gastric cancer as third-line treatment in the US. Nivolumab is also approved in the US for metastatic SCC of the esophagus regardless of PD-L1 expression, and in Japan, South Korea, and Taiwan for the treatment of gastric cancer.

  • The Cancer Genome Atlas analysis has uncovered four genotypes of gastric cancer; however, it is not sufficient to change our treatment strategies, and additional work is needed.

  • A multimodality approach to therapy will be the cornerstone to screening, diagnosing, staging, treating, and supporting patients with upper gastrointestinal cancers.

GASTRIC CANCER

Epidemiologic ...

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